azmiro

Important safety information

Polycythemia : Monitor hematocrit periodically during treatment. Discontinue AZMIRO, if necessary ( 5.1 ). • Venous thromboembolism (VTE) : VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Discontinue AZMIRO if VTE is suspected and initiate appropriate workup and management ( 5.2 ). • Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer : Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. Evaluate patients for prostate cancer, including monitoring prostate specific antigen (PSA) prior to initiating and during treatment with androgens ( 5.3 ). • Blood Pressure Increases : Testosterone can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension ( 5.4 ) • Abuse of Testosterone and Monitoring of Serum Testosterone : If testosterone use at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids is suspected, check serum testosterone concentration ( 5.5 ) • Potential for Adverse Effects on Spermatogenesis : AZMIRO may cause azoospermia ( 5.7 , 8.3 ). • Edema : Edema, with or without congestive heart failure (CHF), may occur in patients with pre-existing cardiac, renal, or hepatic disease. Discontinue AZMIRO and initiate appropriate workup ( 5.9 ). • Sleep Apnea : AZMIRO may potentiate sleep apnea in those with risk factors ( 5.10 ). • Lipid Changes : Testosterone may affect serum lipid profile. Monitor patient lipid concentrations; if necessary, adjust dosage of lipid lowering drug(s) or discontinue AZMIRO ( 5.12 ). • Adverse Effects on Bone Maturation : Testosterone may result in acceleration of bone age and premature closure of epiphyses in pediatric patients which may result in compromised adult stature. Monitor the effect on bone maturation by assessing bone age of the wrist and hand every 6 months. 5.1 Polycythemia Increases in hematocrit levels, reflective of increases in red blood cell mass, may require discontinuation of AZMIRO. Check that hematocrit is not elevated prior to initiating AZMIRO. Periodically monitor hematocrit levels during treatment. If hematocrit becomes elevated, stop AZMIRO until hematocrit decreases to an acceptable concentration. If AZMIRO is restarted and again causes hematocrit to become elevated, stop AZMIRO permanently. An increase in red blood cell mass may increase the risk of thromboembolic events [ see Warnings and Precautions ( 5.2 ) ]. 5.2 Venous Thromboembolism (VTE) There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone replacement products, such as AZMIRO. In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo controlled, cardiovascular (CV) outcomes study, compared to placebo, topical testosterone gel was associated with a numerically higher incidence of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE events (0.9% vs 0.5%) [see Adverse Reactions ( 6.1 )] . Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with AZMIRO and initiate appropriate workup and management [see Adverse Reactions ( 6.2 )] . 5.3 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer • Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. • Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [ see Contraindications ( 4 ) ]. 5.4 Blood Pressure Increases Testosterone products, such as AZMIRO, can increase blood pressure. Blood pressure increases can increase cardiovascular (CV) risk over time. The CV risk associated with topical testosterone gel was evaluated in TRAVERSE, randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, topical testosterone gel increased mean systolic blood pressure by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for topical testosterone gel vs 7.3% for placebo) [See Adverse Reactions ( 6.1 )] . Monitor blood pressure periodically in men using AZMIRO, especially men with hypertension. AZMIRO is not recommended for use in patients with uncontrolled hypertension. 5.5 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [ see Drug Abuse And Dependence ( 9 ) ]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. 5.6 Not for Use in Women Due to lack of controlled studies in women and the potential for virilizing effects, AZMIRO is not indicated for use in women [ see Use in Specific Populations ( 8.1 , 8.2 ) ]. 5.7 Potential for Adverse Effects on Spermatogenesis With large doses of exogenous androgens, including AZMIRO, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) possibly leading to adverse effects on semen parameters including sperm count [ see Use in Specific Populations ( 8.3 ) and Adverse Reactions ( 6.2 ) ]. Patients should be informed of this possible risk when deciding whether to use or to continue to use AZMIRO. 5.8 Hepatic Adverse Effects Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AZMIRO is not a 17 alpha-alkyl androgen and is not known to produce hepatic adverse effects associated with 17-alpha-alkyl androgens. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue AZMIRO while the cause is evaluated. 5.9 Edema Androgens, including AZMIRO, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease [ see Adverse Reactions ( 6.2 ) ]. In addition to discontinuation of the drug, appropriate work up and management of edema may be required. 5.10 Sleep…